Remineralizing and Desensitizing Compositions, Treatments and Methods of Manufacture

ABSTRACT

Improved remineralizing and desensitizing compositions containing remineralizing ingredients in aqueous-free emulsions that, in the presence of saliva, form mucoadhesive gels substantive to tooth surfaces; wherein the gels are dissolved by saliva gradually releasing remineralizing ingredients onto tooth surfaces, treatments with these compositions and methods of manufacture.

FIELD OF THE INVENTION

The present invention is directed to an advance in remineralizing anddesensitizing compositions, whereby the remineralizing and desensitizingingredients are substantive to tooth surfaces, thereby extending theremineralizing or desensitizing process and corresponding remineralizingor desensitizing effectiveness. Key remineralizing and desensitizingingredients include: various fluorides, amorphous calcium phosphate(ACPF) mixtures, bioglass (NovaMin®), tricalcium phosphate fluoridemixtures, etc.

BACKGROUND OF THE INVENTION

ACPF remineralizing/desensitizing compositions and theirremineralizing/desensitizing effects are a preferred embodiment of thepresent invention. ACPF mixtures are presently marketed under the ENAMELPRO® brand.

Remineralizing/desensitizing compositions marketed commercially that areuseful in the present invention include: ACPF mixtures, bioglasscompositions marketed under the trademark, NovaMin®; tricalciumphosphate fluoride mixtures marketed under the trademark, Clinpro™;various fluoride compositions marketed under trademarks including:GELKAM®, Prevident®, Periogard®, etc.

“Washout” of remineralizing/desensitizing ingredients from toothsurfaces by saliva flow, eventually controls the effective residencetime of various commercial, remineralizing/desensitizing ingredients ontooth surfaces, controlling the remineralizing/desensitizingeffectiveness of the various remineralizing/desensitizing ingredientspresently marketed and/or described in the prior art. To improveremineralizing/desensitizing effectiveness, commercial, professionallyprescribed, fluoride remineralizing/desensitizing compositions resort tohigh levels of fluoride, i.e. 5000 ppm for Rx toothpastes, gels andrinses and to approximately 19,000 ppm fluoride for “in-chair”professionally applied varnishes. In contrast, standard OTCremineralizing/desensitizing toothpastes, etc., contain up to 1500 ppmfluoride under the FDA's Fluoride Monograph.

There is a need to improve remineralizing/desensitizing effectivenessfor professional oral care treatments and for OTC products for patientuse, while reducing the risk associated with exposure to high fluoridelevels. For the balance of this specification, the term “remineralizing”is used to describe both “remineralizing and desensitizing” treatments.

OBJECTS OF THE PRESENT INVENTION

An object of the present invention is to improve the remineralizingeffectiveness of various remineralizing ingredients including: ACPFmixtures, bioglass, tricalcium phosphate, fluoride mixtures and variousfluorides in: gels, prophy pastes, rinses, chewing gums, interproximaldevices, etc.

Another object of the present invention is to extend the residence timeon tooth surfaces of various remineralizing ingredients used in variousOTC and professional, remineralizing procedures.

A further object of the invention is to improve professional oral care“in-chair” remineralizing procedures.

Yet another object of the invention is to improve remineralizing ofchildren's teeth, while reducing the level of fluoride required for suchremineralizing.

Yet still another object of the invention is to reduce the level offluoride required to effect remineralization of tooth surfaces byextending the residence time of the remineralizing ingredients on toothsurfaces.

Still another object of the invention is to extend the residence time ontooth surfaces of various remineralizing ingredients, while alsocontrolling the rate of release of various remineralizing ingredientsonto tooth surfaces.

A still further object of the invention is to dispense remineralizingingredients on to tooth surfaces in an aqueous-free emulsion such that,when they come in contact with saliva, these ingredients formmucoadhesive gels substantive to tooth surfaces; wherein themucoadhesive gels are subsequently capable of being solubilized bysaliva flow, thereby extending the duration of the remineralizingtreatment.

The remineralizing compositions and the treatments of the presentinvention, as detailed below, are responsive to the objects of theinvention.

SUMMARY OF THE INVENTION

The present invention is directed to improved remineralizingcompositions and to more effective remineralizing treatments fordemineralized tooth surfaces. Active remineralizing ingredients, usefulin the compositions of the invention, include: various fluorides,various amorphous calcium, phosphate fluoride mixtures (ACPF), bioglass(NovaMin®), tricalcium phosphate, fluoride mixtures and combinationsthereof.

More effective remineralizing treatments of the present invention fordemineralized tooth surfaces include various self-applied treatmentswith dental devices, toothpastes, gels, rinses, chewing gum, lozenges,etc., containing compositions of the present invention; as well asvarious professional “in-chair” procedures including varnishes, gels,rinses, etc., with professional versions of the compositions of theinvention.

The remineralizing compositions of the present invention andremineralizing treatments of the present invention utilize anaqueous-free emulsion containing various remineralizing ingredients,wherein the emulsion in the presence of saliva forms a mucoadhesive gelthat is substantive to tooth surfaces. The substantive, mucoadhesive gelslowly dissolves in the presence of saliva, gradually releasingremineralizing ingredients, onto tooth surfaces. This slow release ofremineralizing ingredients continues until the mucoadhesive gel iseventually totally solubilized by saliva. This gradual release ofremineralizing ingredients from the mucoadhesive gel minimizes the“wash-out” effect of remineralizing ingredients characteristic ofcommercial remineralizing products and associated commercial treatmentspresently available.

The resultant “extended” remineralizing feature of the compositions andtreatments of the present invention represent a major advance ineffective remineralizing, along with reduced risk associated with lowerlevels of fluoride, required to effect remineralization.

ACP/aqueous-free emulsion compositions and ACPF/aqueous-free emulsioncompositions are preferred embodiments of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

The substantivity of the aqueous-free emulsion containing activeingredient, in the presence of water, is demonstrated visually by theDrawings included herein, where:

FIGS. 1 through 8 are photographs of three separate microscope slides,each coated with a different remineralizing toothpaste. All three slidesare submersed in separate beakers containing water. The photographsindicate various levels of substantivity of the three toothpastes atvarious time periods.

FIGS. 9 through 11 are photographs of a microscope slide coated with anaqueous-free emulsion coating showing conversion of a mucoadhesive gelupon the addition of water.

DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS

Aqueous-free emulsions of the present invention that serve as carriersfor various remineralizing ingredients are characterized by theirability, in the presence of saliva, to form mucoadhesive gels which aresubstantive to tooth surfaces. These substantive, mucoadhesive gels ofthe present invention are further characterized by their ability to: (a)gradually dissolve when exposed to saliva flow, and (b) graduallyrelease various remineralizing ingredients onto tooth surfaces. Thisgradual dissolution feature of mucoadhesive gels of the presentinvention minimizes saliva “wash-out” of remineralizing ingredients byeffecting a gradual slow release of remineralizing ingredients ontotooth surfaces. The substantive, mucoadhesive gels of the presentinvention extend the duration of remineralizing of tooth surfaces undertreatment; thereby enhancing the effectiveness of various remineralizingtreatments of the present invention, while reducing the level offluoride required to achieve effective remineralization.

All of the references cited herein, are hereby, in their entirety,incorporated by reference into the present invention.

The Role of ACPF Mixtures in Remineralizing Tooth Surfaces

The remineralizing properties of the preferred amorphous calciumphosphate fluoride mixtures (ACPF) of the present invention aredescribed: by Ming Tung in U.S. Pat. Nos. 5,037,639; 5,268,167;5,427,768; 5,437,857; 5,460,803; 5,562,895; by Tung in the AmericanDental Association Foundation publication, “ACP Technology,”; bySchemahorn, et. al., in The Journal of Clinical Dentistry Vol. XXII: No2. 51-54, 2011; and by the 19 references cited by Schemahorn, et. al.

In addition, amorphous calcium phosphate is described by Wikipedia asfollows:

-   -   “Amorphous calcium phosphate (ACP) is a substance used as a        dental treatment. Calcium and phosphate are natural building        blocks of teeth, and when present in insufficient amounts, there        can be sensitivity after procedures such as dental bleaching or        professional dental cleansing. Amorphous calcium phosphate will        help in restoring the necessary mineral balance in the mouth in        an easy and efficient way.    -   “ACP technology using a two-phase delivery system that prevents        the calcium and phosphate from reacting was developed by Ming S.        Tung at the American Dental Research Association's Paffenbarger        Research Center. It was first used in a toothpaste called        Enamelon in 1999, but it failed commercially. It is now found in        Arm & Hammer's Enamel Care Toothpaste (introduced in 2004) as        well as their Age Defying Toothpaste, Discus Dental's Nite White        bleaching gel, Discus Dental's Relief ACP sensitivity relief        product, and Premier Dental's Enamel Pro polishing paste. It is        also used in the Aegis product line, such as Aegis® Pit and        Fissure Sealant with ACP, produced by the Harry J. Bosworth        Company for use by dental professionals. Other Aegis Products        include: Aegis® Orthodontic Adhesive with ACP, Aegis® Liner with        ACP, Aegis® V with ACP and Aegis® Crown and Bridge with ACP.”

According to Ming Tung, after the ACPF salts in the aqueous-freeemulsions are dissolved in saliva, they precipitate and hydrolyze totooth mineral as follows: In an acidic environment, the followingreactions occur rapidly; leading to remineralization of tooth surfacesthat have been physically cleaned:

-   -   The Ca²⁺ and X²⁺(HPO₄)²⁻+F⁻ ions precipitate as CaF₂Ca₉X(PO₄)₆F₂        (ACXPF).

Subsequent hydrolysis of this precipitate releases fluoridated toothmineral:

Ca₁₀(PO₄)₆F₂+F⁻+(H_(1.5)PO₄)^(1.5−)+OH+X²⁴

Preferred ACPF, Aqueous-free emulsions of the present invention,contain:

-   -   calcium gluconate,    -   calcium lactate, gluconate,    -   disodium hydrogen phosphate,    -   sodium fluoride, and    -   citric acid, or ascorbyl palmitate.

The aqueous-free emulsions of the present invention hold the variousremineralizing salts in suspension without the salts reacting. When thisaqueous-free emulsion is exposed to saliva, it forms a mucoadhesive gelthat is substantive to tooth surfaces. This mucoadhesive gel continuesto hold the various remineralizing ingredients without the ingredientsreacting.

Eventually, this mucoadhesive gel is dissolved by saliva, releasing theunreacted ACPF components onto the hydroxyapatite. The ACPF componentspenetrate the hydroxyapatite, subsequently forming amorphous calciumphosphate fluoride precipitates within the hydroxyapatite.

Remineralizing, functional, aqueous-free emulsions of the presentinvention contain stable cations and stable anions, suitable forsubsequently reacting to remineralize dental enamel; wherein:

-   -   (1) said aqueous-free emulsion inhibits premature reaction of        the cations with the anions;    -   (2) the cations and anions are introduced onto tooth surfaces        via saliva soluble, mucoadhesive gels that are substantive to:        hydroxyapatite, dentin, biofilm, pellicle, soft tissue, etc.;    -   (3) the cations and anions are gradually released onto the        hydroxyapatite as the saliva soluble, mucoadhesive gels undergo        dissolution at rates generally controlled by saliva flow;    -   (4) local saliva flow can be further controlled by saliva        enhancers such as spilanthes extract, which are introduced onto        tooth surfaces from said aqueous-free emulsion;    -   (5) local pH environment for said dissolving gels is controlled,        in part, by pH controlling compositions, such as: ascorbyl        palmitate, citric acid, etc., present in said aqueous-free        emulsion, where the pH controlling composition also assists in        substantivity of the various cations and anions released onto        tooth surfaces upon dissolution of said mucoadhesive gels;    -   (6) said saliva soluble gel controls the rate of release of        cations onto tooth surfaces, thereby controlling diffusion of        said cations into demineralized subsurfaces and/or into dentinal        tubules;    -   (7) said saliva soluble gel also controls rate of release of        anions onto tooth surfaces, thereby controlling diffusion of        said anions into demineralized subsurfaces and/or into exposed        tubules;    -   (8) said solubilized cations and anions, after diffusing into        demineralized subsurfaces and/or into exposed tubules: react and        precipitate in an amorphous state remineralizing hydroxyapatite;    -   (9) said aqueous-free emulsion comprises polydimethylsiloxane,        at various molecular weights emulsified in nonionic surfactants        comprised of copolymers comprised of polyoxypropylene and        polyoxyethylene that form mucoadhesive gels in the presence of        saliva; and    -   (10) said remineralizing, functional, aqueous-free emulsions can        be dispensed via: dental tape, dental floss, toothpaste, prophy        paste, fluoride varnishes, fluoride gels, dry mouth gels and        combinations thereof.

For purposes of the present invention, saliva soluble, aqueous-freeemulsions ingredients include those emulsions that are comprised ofpolydimethylsiloxane in a nonionic surfactant, as described in thefollowing U.S. Pat. Nos. 5,032,387; 5,098,711; 5,538,667 and 5,651,959;all of which are hereby incorporated by reference. Only thoseaqueous-free emulsions described in the referenced U.S. patents thatform mucoadhesive gels substantive to tooth surfaces are useful forpurposes of the present invention.

Preferred nonionic surfactants of the present invention capable offorming mucoadhesive gels in the presence of saliva, are selected fromthe group consisting of: poloxamer 237, poloxamer 338, poloxamer 407 andcombinations thereof.

Preferred aqueous-free, saliva soluble emulsions for use in theremineralizing compositions of the present invention include emulsionsof polydimethylsiloxane (PDMS) at viscosities ranging from between about1500 cs and about 2.5 million cs. Particularly preferred, aqueous-freeemulsions include as the discontinuous phase PDMS at viscosities between10,500 cs and 2.5 million cs with those nonionic surfactants describedin detail in U.S. Pat. No. 5,651,959 that form mucoadhesive gels in thepresence of saliva, as the continuous phase.

Preferred polydimethylsiloxanes are selected from the group consistingof polydimethylsiloxane: at 1500 cs, at 12,500 cs, at 100,000 cs, at250,000 cs, at 500,000 cs, at 750,000 cs, at 1.5 million cs, at 2.2million cs, at 2.5 million cs and combinations thereof.

Preferred application means for the remineralizing compositions of thepresent invention include: oral gels, oral ointments, oral pastes, oralvarnishes, toothpastes, oral liquids, lozenges, chewing gums and variousinterproximal devices coated with said remineralizing compositions.

The present invention is further described and illustrated in examples 1through 29, which describe certain embodiments of the invention, whilealso suggesting other uses for the invention.

Examples 1 to 9 PROPHY TAPE® with ULTRAMULSION® & ACPF Example 1 ACPFPROPHY TAPE®

A 2 gallon stainless steel vessel was fitted with an overhead stirrerand place on a hotplate. An aqueous-free emulsion comprising poloxamer407/polydimethylsiloxane (12,500 cs) 90:10; 945.63 gm and 1200 gm ofpoloxamer 407 were placed in the vessel and melted while stirring. Thetemperature rose to 90 degrees Centigrade and the following ingredientswere added: Pluracare L-1220, 120 gm; stearyl alcohol, 450.8 gm;microwax ML445, 267.6 gm; and PEG 8000, 388 gm, were added to the moltenaqueous-free emulsion. A homogenizer was placed in the vessel andemulsification resulted from 10 minutes of action. The following ACPFingredients were then added with stirring: Calcium gluconate, 240 gm;Calcium lactate gluconate, 84 gm; disodium hydrogen phosphate, 48 gm;sodium fluoride, 4.4 gm; propyl gallate, 4 gm; sodium saccharin, 96 gm;EDTA, 8 gm; flavor, 104 gm; and citric acid, 40 gm. The emulsified tapecoating batter was then dispensed into the tape coating tank.Compression coating of ultra-high-molecular-weight polyethylene dentaltape at 67 mg/yard was completed to give a saliva soluble, coated,dental tape with amorphous calcium phosphate fluoride effects. The tapewas overcoated with pumice at between 6 and 10 gm/yd and post-flavoredvia flavor transfer from a flavor reservoir.

Following the procedures set out in Example 1, PROPHY TAPE® Examples 2through 9, as detailed in Table 1 below, were prepared. All PROPHYTAPES® were overcoated with pumice abrasive and post-flavored via flavortransfer from a flavor reservoir in a flavor-sealed package.

TABLE 1 ACPF PROPHY TAPE ® EXAMPLES 2 through 9 ACPF Ingredients (all %by wt.) Example Aqueous-free Gluconate Calcium Disodium Sodium #Emulsion Phosphate Lactate Hydrogen Fluoride 2 23.81 7.5 2.62 1.5 0.09 326.7 5 1.74 1.0 0.05 4 11 7.5 2.62 1.5 0.138 5 5 7.5 2.62 1.5 0.138 6 115 1.74 1.0 0.09 7 5 5 1.74 1.0 0.09 8 11 2.5 0.873 0.5 0.05 9 5 2.50.873 0.5 0.05

Illustrative Examples 10 Through 24

Examples summarized in Tables 2 through 4 below, further illustrate thebroad range of improved remineralizing compositions, in variousdispensing means.

All of the illustrative remineralizing Examples, set out Tables 2through 4, are to be formulated to form mucoadhesive gels when dispensedin the presence of saliva, which mucoadhesive gels are substantive totooth surfaces and capable of gradual dissolution upon continuousexposure to saliva.

Following the procedures in Example 1, the aqueous-free emulsioncompositions can be prepared and used for coating PROPHY TAPE®, PTFEdental tape and multifilament dental floss, as detailed in Examples 10through 14 in Table 2 below.

TABLE 2 Illustrative Examples 10 through 14 PROPHY TAPE ®, PTFE DentalTape, Multifilament Dental Floss Reminerali- Saliva Exam- Composition ofzation Enhancement ple Aqueous-free Ingredients Ingredient Dispensing #Emulsion (% by wt.) (% by wt.) means 10 PDMS Bioglass SpilanthesMultifilament (2.5 mm cs) (7.5) Extract dental floss 10% in (0.6) withbase poloxamer 407 coating at 24% between 40 and 60 mg/yd 11 PDMSTricalcium Spilanthes Multifilament (2.5 mm cs) Phosphate Extract dentalfloss 20% in (5) (0.2) with base poloxamer 407 Sodium coating at 15%Fluoride between 50 (1.1) and 70 mg/yd 12 PDMS Stannous Spilanthes PTFEdental (12,500 cs) Fluoride Extract tape with 20% in (2.06) (0.15) basecoating poloxamer 407 between 50 at 25% and 70 mg/yd 13 PDMS SodiumSpilanthes PROPHY (2.5 mm cs) mono- Extract TAPE ® with 10% in fluoro-(0.4) base coating poloxamer 338 phosphate between 55 at 25% (3.78) and75 mg/yd 14 PDMS Sodium Spilanthes PROPHY (2.5 mm cs) fluoride extractTAPE ® with 20% in (1.11) (0.1) base coating poloxmer 407 between 60 at20% and 80 mg/yd

Following the procedure in Example 1, the remineralizing, aqueous-freeemulsion compositions described in Examples 15 through 19 in Table 3below can be prepared for use in Prophy Pastes, and various alternativesto Prophy Pastes.

TABLE 3 Illustrative Examples 15 through 19 Composition of Reminerali-Saliva Exam- Aqueous free zation Enhancement Dis- ple EmulsionIngredients Ingredient pensing # (% by wt.) (% by wt.) (% wt.) Means 15PDMS Bioglass Spilanthes prophy (2.5 mm cs) (5) extract paste 35% in(0.4) poloxamer 407 at 1% 16 PDMS tricalcium Spilanthes prophy (2.5mmcs) phosphate extract paste 10% in (5) and (0.25) poloxamer 338 Sodiumat 3% Fluoride (1.1) 17 PDMS stannous Spilanthes prophy (2.5mm cs)fluoride extract paste 35% in (2.1) (0.1) poloxamer 407 1.5% 18 PDMSsodium Spilanthes prophy (2.5 mm cs) mono- extract paste 35% in fluoro-(0.12) poloxamer 407 phosphate at 1% (3.79) 19 PDMS sodium Spilanthesprophy (2.5 mm cs) fluoride extract paste 35% in (1.1) (0.3) poloxamer338 at 1%

Examples 20 Through 24

Following the procedures in Example 1, the aqueous-free emulsioncompositions can be prepared and used for toothpaste, as detailed inExample 20 through 25 of Table 4.

TABLE 4 Illustrative Examples 20 through 25 Composition of Reminerali-Saliva Exam- aqueous-free zation enhancement Dis- ple emulsioningredients ingredient pensing # (% by wt.) (% by wt.) (% by wt.) Means20 PDMS Bioglass Spilanthes Tooth- (2.5 mm cs) (6.0) Extract paste 20%in (0.12) poloxamer 407 3% 21 PDMS Tricalcium Spilanthes Tooth- (2.5 mmcs) phosphate extract paste 10% in (5) and (0.1) poloxamer 407 Sodium 3%fluoride (1.1) 22 PDMS Stannous Spilanthes Tooth- (2.5 mm cs) fluorideextract paste 20% in (2.06) (0.2) poloxmer 338 2% 23 PDMS SodiumSpilanthes Tooth- (2.5 mm cs) mono- extract paste 20% in fluoro- (0.25)poloxamer 407 phosphate 2.5% (3.79) 24 PDMS Sodium Spilanthes Tooth-(2.5 mm cs) fluoride extract paste 10% in (1.1) (0.1) poloxamer 338 2%25 PDMS ACP Spilanthes Children's (2.5 mm cs) (5.0) extract Fluoride-10% in (0.1) free poloxamer 407 Tootpaste 2%

Example 26 Multifilament Dental Floss with ACPF

A 3 gallon stainless steel vessel was fitted with an overhead stirrerand a hot plate. The following ingredients were added with stifling andheating to 90 degrees Centigrade: an aqueous-free emulsion (poloxamer407, 2673.7 gm; silicone AF1500, 400 gm); sodium saccharin, 92 gm;propyl gallate, 4 gm; silica, 160 gm; sodium fluoride, 5.52 gm; calciumgluconate, 300 gm; calcium lactate gluconate, 104.8 gm; disodiumhydrogenphosphate, 60 gm; flavor, 160 gm and citric acid, 40 gm. Thevessel was heated and stirred for 20 minutes and the contentstransferred to the dental floss applicator tank. Compression coating ofthe 840 texturized nylon 6,6 yarn produced a dental floss with a coatinglevel of 84 mg/yd. Prior to flossing, the multifilament floss isstretched and released, allowing the texturized floss to expand therebyoptimizing interproximal delivery of calcium, phosphate and fluoride totooth surfaces while leaving a clean just-brushed feeling.

Example 27 Children's Fluoride-Free Toothpaste with ACP/Aqueous-FreeEmulsion

A Hobart N-50 mixer fitted with a 1 gallon stainless steel bowl was usedto mix the following: PEG 400, 272 gm; an aqueous-free emulsion[poloxamer 407/polydimethyl-siloxane (90:10)], 64 gm; poloxamer 407,80.8 gm; pluracol L-1220, 80.8 gm; Carbopol 974P, 12 gm; glycerin, 584.8gm; xylitol powder, 48 gm; acesulfame K, 4.8 gm; titanium dioxide, 16gm; zeodent, 80 gm; sipernat 22S, 120 gm; perlastin L, 8 gm; sucralose,2.4 gm; flavor, 28 gm, were stirred for 5 minutes at room temperature.The contents of the bowl were heated to 80 degrees Centigrade. Calciumgluconate, 128 gm; calcium lactate gluconate, 44.8 gm and disodiumhydrogenphosphate, 25.6 gm, were then added. After stirring for 10minutes, the content of the one gallon vessel was transferred to 1.5 oztubes. Application of 1.5 gram of the toothpaste to the oral mucosa withbrushing delivers amorphous calcium phosphate, remineralizing effects;relying on mucoadhesive properties of the gel formed on tooth surfacesin the presence of saliva.

Example 28 Adult Toothpaste with ACPF/Aqueous-Free Emulsion

A Hobart N-50 mixer fitted with a 1 gallon stainless steel bowl was usedto mix the following: PEG 400, 272.48 gm; an aqueous-free [poloxamer407/polydimethyl-siloxane (90:10)], 24 gm; Carbopol 974P, 12 gm;glycerin, 744.96 gm; xylitol powder, 80 gm; acesulfame K, 4.8 gm;titanium dioxide, 16 gm; zeodent 113, 80 gm; sipernat 22S, 120 gm;perlastin L, 16 gm; sucralose, 2.4 gm and flavor, 28.8 gm, were stirredfor 5 minutes at room temperature. The contents of the bowl were heatedto 80 degrees Centigrade. Calcium gluconate, 128 gm; calcium lactategluconate, 44.8 gm and disodium hydrogenphosphate, 25.6 gm, were thenadded. After stirring for 10 minutes, the content of the one gallonvessel was transferred into 2 oz tubes. Application of 2 gram of thetoothpaste to the oral mucosa with brushing delivers amorphous calciumphosphate fluoride, remineralizing; relying on the mucoadhesive gelformed on tooth surfaces in the presence of saliva.

Example 29 Comparative Substantivity of Three Toothpastes

An experiment was designed to compare the substantivity properties ofthree toothpastes. A separate microscope slide was utilized assubstrates for each toothpaste. A small bead of toothpaste was appliedto a saliva-coated slide. The bead was leveled with a microscope cloverslip to obtain a thin coating simulating the thin coat a toothbrushmight apply. This procedure was repeated for each of three toothpastesamples. Each slide was immersed in 17 ml of water in a 50 ml beaker.Photographs were taken of side-by-side beakers containing each slidewith the thin layer of test toothpaste submerged in water. Photographsat 0, 1, 3, 4, 5, 10, 15 and 20 minutes show the rapid loss of adhesionfor the NUPRO® SENSODYNE® toothpaste at one minute and similar loss ofadhesion for Clinpro™ 5000 Toothpaste after three minutes. Thesubstantivity of the Children's ACP/ULTRAMULSION® toothpaste to theslide after 20 minutes indicates the substantivity of the mucoadhesivegel that forms in the presence of water or saliva.

The photographs at 0, 1, 3, 4, 5, 10, 15 and 20 minutes are included asFIGS. 1 through 8 of the Drawings.

An Aqueous-Free Emulsion of the Invention Forms a Mucoadhesive Gel

A microscope slide coated with an aqueous-free emulsion of the presentinvention was treated with water. The photographs of the coated slidebefore and after application of water are included as FIGS. 9 through 11of the Drawings.

What is claimed is:
 1. Improved remineralizing and desensitizingcompositions, comprising an aqueous-free emulsion containingremineralizing ingredients; wherein said compositions form mucoadhesivegels, upon contact with saliva, that are substantive to tooth surfaces;and wherein said mucoadhesive gels are slowly solubilized upon ongoingcontact with saliva, continuously releasing said remineralizing anddesensitizing ingredients onto tooth surfaces to effect extendedremineralization and desensitization of said tooth surfaces, with aminimum of saliva “wash-out” of said remineralizing and desensitizingingredients.
 2. Improved remineralizing and desensitizing compositionsthat are substantive to tooth surfaces and that extend the duration ofremineralizing and desensitizing treatments comprising: an aqueous-freeemulsion containing dispensed therein various remineralizing anddesensitizing ingredients wherein: said aqueous-free emulsion in thepresence of saliva, forms a mucoadhesive gel substantive to said toothsurfaces, said substantive, mucoadhesive gel gradually dissolves in thepresence of saliva, releasing onto said tooth surfaces, saidremineralizing and desensitizing ingredients, and said slowly releasedremineralizing ingredients continue to remineralize said tooth surfacesuntil said substantive mucoadhesive gel is solubilized by said salivaflow, thereby extending the duration of said remineralizing anddesensitizing and effecting improved remineralization anddesensitization of said tooth surfaces.
 3. An improved remineralizingcomposition according to claim 2, wherein said remineralizingingredients are selected from the group consisting of: variousfluorides, various amorphous calcium phosphate fluoride combinations,bioglass, tricalcium phosphate fluoride mixtures and combinationsthereof.
 4. An improved remineralizing composition according to claim 2,wherein said aqueous-free emulsion contains polydimethylsiloxane as thediscontinuous phase and nonionic poloxamer surfactants as the continuousphase.
 5. An improved remineralizing composition according to claim 4,wherein said polydimethylsiloxane discontinuous phase has a viscositybetween about 1500 cs and about 2.5 million cs.
 6. An improvedremineralizing composition according to claim 4, wherein said nonionicsurfactant continuous phase comprises nonionic poloxamer surfactantsthat form mucoadhesive gels in the presence of saliva, wherein said gelsare substantive to tooth surfaces.
 7. An improved remineralizingcomposition according to claim 6, wherein said nonionic surfactant isselected from the group consisting of: poloxamers, polysorbates,poloxyethylene alcohols and combinations thereof.
 8. An improvedremineralizing composition according to claim 3, wherein said amorphouscalcium phosphate fluoride combinations comprise mixtures selected fromthe group consisting of: calcium gluconate, calcium lactate gluconate,calcium nitrate, calcium sulfate and combinations thereof.
 9. Improvedremineralizing compositions according to claim 1, wherein dispensingmeans for said improved remineralizing compositions are selected fromthe group consisting of: interproximal devices coated with saidcompositions, prophy paste, varnish, gel, toothpaste, chewing gum,sealant, rinse, and combinations thereof.
 10. Improved remineralizingcompositions of the invention according to claim 2, wherein thesubstantivity of said mucoadhesive gel is improved by the addition ofcompositions selected from the group consisting of: poloxamers,carboxymethyl cellulose, carbopol, gantrez, carrageenan gum, tragacanthgum, xanthan gum, guar gum and combinations thereof.
 11. An improvedremineralizing composition according to claim 8, wherein the pH of saidamorphous calcium phosphate fluoride combinations released onto toothsurfaces is adjusted by the addition of pH control compositions selectedfrom the group consisting of: citric acid, ascorbic acid, phosphoricacid, malic acid and combinations thereof.
 12. An improvedremineralizing composition according to claim 2, wherein said salivaflow is enhanced by the addition of saliva enhancing compositionsselected from the group consisting of: Jambu resin, spilanthes extract,spilanthol and combinations thereof.
 13. An improved remineralizingcomposition according to claim 1, wherein said mucoadhesive gels are asshown in FIG. 1 through 8 of the Drawings.
 14. Improved remineralizingcompositions according to claim 1, wherein said remineralizingingredients include commercial versions from the group consisting of:various fluorides, various ACPF mixtures, various bioglass fluoridemixtures, various tricalcium phosphate fluoride mixtures andcombinations thereof.
 15. An improved desensitizing compositionaccording to claim 2, wherein said desensitizing ingredients areselected from the group consisting of: various fluorides, variousamorphous calcium phosphate fluoride combinations, bioglass, tricalciumphosphate fluoride mixtures and combinations thereof.
 16. An improveddesensitizing composition according to claim 2, wherein saidaqueous-free emulsion contains polydimethylsiloxane as the discontinuousphase and nonionic poloxamer surfactants as the continuous phase.
 17. Animproved desensitizing composition according to claim 16, wherein saidpolydimethylsiloxane discontinuous phase has a viscosity between about1500 cs and about 2.5 million cs.
 18. An improved desensitizingcomposition according to claim 16, wherein said nonionic surfactantcontinuous phase comprises nonionic poloxamer surfactants that formmucoadhesive gels in the presence of saliva, wherein said gels aresubstantive to tooth surfaces.
 19. An improved desensitizing compositionaccording to claim 18, wherein said nonionic surfactant is selected fromthe group consisting of: poloxamers, polysorbates, poloxyethylenealcohols
 20. An improved desensitizing composition according to claim15, wherein said amorphous calcium phosphate fluoride combinationscomprise mixtures selected from the group consisting of: calciumgluconate, calcium lactate gluconate, calcium nitrate, calcium sulfateand compositions thereof.
 21. Improved desensitizing compositionsaccording to claim 1, wherein dispensing means for said improveddesensitizing compositions are selected from the group consisting of:interproximal devices coated with said compositions, prophy paste,varnish, gel, toothpaste, chewing gum, sealant, rinse, and combinationsthereof.
 22. Improved desensitizing compositions of the inventionaccording to claim 2, wherein the substantivity of said mucoadhesive gelis improved by the addition of compositions selected from the groupconsisting of: poloxamers, carboxymethyl cellulose, carbopol, gantrez,carrageenan gum, tragacanth gum, xanthan gum, guar gum and combinationsthereof.
 23. An improved desensitizing composition according to claim19, wherein the pH of said amorphous calcium phosphate fluoridecombinations released onto tooth surfaces is adjusted by the addition ofpH control compositions selected from the group consisting of: citricacid, ascorbic acid, phosphoric acid, malic acid and combinationsthereof.
 24. An improved desensitizing composition according to claim 2,wherein said saliva flow is enhanced by the addition of saliva enhancingcompositions selected from the group consisting of: Jambu resin,spilanthes extract, spilanthol and combinations thereof.
 25. An improveddesensitizing composition according to claim 1, wherein saidmucoadhesive gels are as shown in FIG. 1 through 8 of the Drawings. 26.Improved desensitizing compositions according to claim 1, wherein saiddesensitizing ingredients include commercial versions from the groupconsisting of: various fluorides, various ACPF mixtures, variousbioglass fluoride mixtures, various tricalcium phosphate fluoridemixtures and combinations thereof.
 27. Improved, remineralizing,interproximal devices, comprising an aqueous-free emulsion coatingscontaining remineralizing ingredients; wherein said coatingcompositions, released during flossing, form mucoadhesive gels, uponcontact with saliva, that are substantive to tooth surfaces; and whereinsaid mucoadhesive gels are slowly solubilized upon ongoing contact withsaliva, continuously releasing said remineralizing ingredients ontotooth surfaces to effect extended remineralization of interproximaltooth surfaces, with a minimum of saliva “wash-out” of saidremineralizing ingredients.
 28. Improved, remineralizing, interproximaldevices containing aqueous-free coating compositions that release duringflossing, are substantive to tooth surfaces and that extend the durationof interproximal, remineralizing treatments comprising: an aqueous-freeemulsion coating, containing dispensed therein various remineralizingingredients wherein: said aqueous-free emulsion coating, in the presenceof saliva, forms a mucoadhesive gel substantive to said interproximaltooth surfaces, said substantive, mucoadhesive gel gradually dissolvesin the presence of saliva, releasing onto said interproximal toothsurfaces, said remineralizing ingredients, and said slowly releasedremineralizing ingredients continue to remineralize said interproximaltooth surfaces until said substantive mucoadhesive gel is solubilized bysaid saliva flow, thereby extending the duration of said remineralizingand effecting improved remineralization of said interproximal toothsurfaces.
 29. An improved, remineralizing, interproximal device coatingaccording to claim 28, wherein said remineralizing ingredients areselected from the group consisting of: various fluorides, variousamorphous calcium phosphate fluoride combinations, bioglass, tricalciumphosphate fluoride mixtures and combinations thereof.
 30. An improved,remineralizing, interproximal device coating according to claim 28,wherein said aqueous-free emulsion coating contains polydimethylsiloxaneas the discontinuous phase and nonionic poloxamer surfactants as thecontinuous phase.
 31. An improved, remineralizing, interproximal devicecoating according to claim 30, wherein said polydimethylsiloxanediscontinuous phase has a viscosity between about 1500 cs and about 2.5million cs.
 32. An improved, remineralizing, interproximal devicecoating according to claim 30, wherein said nonionic surfactantcontinuous phase comprises nonionic poloxamer surfactants that formmucoadhesive gels in the presence of saliva, wherein said gels aresubstantive to tooth surfaces.
 33. An improved, remineralizing,interproximal device coating according to claim 32, wherein saidnonionic surfactant is selected from the group consisting of:poloxamers, polysorbates, poloxyethylene alcohols and combinationsthereof.
 34. An improved, remineralizing, interproximal device coatingaccording to claim 29, wherein said amorphous calcium phosphate fluoridecombinations comprise mixtures selected from the group consisting of:calcium gluconate, calcium lactate gluconate, calcium nitrate, calciumsulfate and combinations thereof.
 35. Improved, remineralizing,interproximal device coatings according to claim 27, wherein dispensingmeans for said improved, remineralizing, interproximal devices areselected from the group consisting of: monofilament, interproximaldevices; multifilament, interproximal devices; one-handed flossers,dental stimulators and combinations thereof, coated with saidcompositions.
 36. Improved, remineralizing, interproximal device,coating compositions of the invention, according to claim 28; whereinthe substantivity of said mucoadhesive gel is improved by the additionof compositions selected from the group consisting of: poloxamers,carboxymethyl cellulose, carbopol, gantrez, carrageenan gum, tragacanthgum, xanthan gum, guar gum and combinations thereof.
 37. An improved,remineralizing, interproximal device containing compositions, accordingto claim 34; wherein the pH of said amorphous calcium phosphate fluoridecombinations released onto interproximal tooth surfaces is adjusted bythe addition of pH control compositions selected from the groupconsisting of: citric acid, ascorbic acid, phosphoric acid, malic acidand combinations thereof.
 38. An improved, remineralizing, interproximaldevice coating composition, according to claim 28; wherein said salivaflow is enhanced by the addition of saliva enhancing compositionsselected from the group consisting of: Jambu resin, spilanthes extract,spilanthol and combinations thereof.
 39. An improved, remineralizing,interproximal device, coating composition, according to claim 27;wherein said mucoadhesive gels are as shown in FIG. 1 through 8 of theDrawings.
 40. Improved, remineralizing, interproximal device, coatingcompositions, according to claim 27; wherein said remineralizingingredients include commercial versions from the group consisting of:various fluorides, various ACPF mixtures, various bioglass fluoridemixtures, various tricalcium phosphate fluoride mixtures andcombinations thereof.
 41. Improved, desensitizing, interproximaldevices, comprising aqueous-free, emulsion coatings containingdesensitizing ingredients; wherein said coating compositions arereleased during flossing and form mucoadhesive gels, upon contact withsaliva, that are substantive to tooth surfaces; and wherein saidmucoadhesive gels are slowly solubilized upon ongoing contact withsaliva, continuously releasing said desensitizing ingredients ontointerproximal tooth surfaces to effect extended desensitization of saidinterproximal tooth surfaces, with a minimum of saliva “wash-out” ofsaid desensitizing ingredients.
 42. Improved, desensitizing,interproximal devices containing aqueous-free, coating compositions thatrelease during flossing, are substantive to interproximal tooth surfacesand that extend the duration of interproximal desensitizing treatmentscomprising: an aqueous-free, emulsion coating containing dispensedtherein various desensitizing ingredients wherein: said aqueous-free,emulsion coating in the presence of saliva, forms a mucoadhesive gelsubstantive to said interproximal tooth surfaces, said substantive,mucoadhesive gel gradually dissolves in the presence of saliva,releasing onto said interproximal tooth surfaces, said desensitizingingredients, and said slowly released desensitizing ingredients continueto desensitize said interproximal tooth surfaces until said substantivemucoadhesive gel is solubilized by said saliva flow, thereby extendingthe duration of said desensitizing and effecting improveddesensitization of said interproximal tooth surfaces.
 43. An improved,desensitizing, interproximal device coating according to claim 42,wherein said desensitizing ingredients are selected from the groupconsisting of: various fluorides, various amorphous calcium phosphatefluoride combinations, bioglass, tricalcium phosphate fluoride mixturesand combinations thereof.
 44. Improved, desensitizing, interproximaldevice coatings according to claim 42, wherein said aqueous-free,emulsion coating contains polydimethylsiloxane as the discontinuousphase and nonionic poloxamer surfactants as the continuous phase.
 45. Animproved, desensitizing, interproximal device coating according to claim44, wherein said polydimethylsiloxane discontinuous phase has aviscosity between about 1500 cs and about 2.5 million cs.
 46. Animproved, desensitizing, interproximal device coating according to claim44, wherein said nonionic surfactant continuous phase comprises nonionicpoloxamer surfactants that form mucoadhesive gels in the presence ofsaliva, wherein said gels are substantive to interproximal toothsurfaces.
 47. An improved, desensitizing, interproximal device coatingaccording to claim 46, wherein said nonionic surfactant is selected fromthe group consisting of: poloxamers, polysorbates, poloxyethylenealcohols and combinations thereof.
 48. An improved, desensitizing,interproximal device coating according to claim 43, wherein saidamorphous calcium phosphate fluoride combinations comprise mixturesselected from the group consisting of: calcium gluconate, calciumlactate gluconate, calcium nitrate, calcium sulfate and combinationsthereof.
 49. Improved desensitizing, interproximal device, coatingcompositions according to claim 41, wherein dispensing means for saidimproved desensitizing interproximal devices are selected from the groupconsisting of: monofilament, interproximal devices; multifilament,interproximal devices; one-handed flossers; dental stimulators andcombinations thereof; coated with said compositions.
 50. Improved,desensitizing, interproximal device, coating compositions of theinvention according to claim 42, wherein the substantivity of saidmucoadhesive gel is improved by the addition of compositions selectedfrom the group consisting of: poloxamers, carboxymethyl cellulose,carbopol, gantrez, carrageenan gum, tragacanth gum, xanthan gum, guargum and combinations thereof.
 51. An improved, desensitizing,interproximal device, coating composition according to claim 48, whereinthe pH of said amorphous calcium phosphate fluoride combinationsreleased onto interproximal tooth surfaces is adjusted by the additionof pH control compositions selected from the group consisting of: citricacid, ascorbic acid, phosphoric acid, malic acid and combinationsthereof.
 52. Improved, desensitizing, interproximal device, coatingcompositions according to claim 42, wherein said saliva flow is enhancedby the addition of saliva enhancing compositions selected from the groupconsisting of: Jambu resin, spilanthes extract, spilanthol andcombinations thereof.
 53. Improved, desensitizing, interproximal device,coating compositions according to claim 41, wherein said mucoadhesivegels are as shown in FIG. 1 through 8 of the Drawings.
 54. Improved,desensitizing, interproximal device, coating compositions according toclaim 42, wherein said desensitizing ingredients include commercialversions from the group consisting of: various fluorides, various ACPFmixtures, various bioglass fluoride mixtures, various tricalciumphosphate fluoride mixtures and combinations thereof.
 55. Improvedmethods for remineralizing, comprising treating tooth surfaces with anaqueous-free emulsion containing remineralizing ingredients; whereinsaid compositions form mucoadhesive gels, upon contact with saliva, thatare substantive to tooth surfaces; and wherein said mucoadhesive gelsare slowly solubilized upon ongoing contact with saliva, continuouslyreleasing said remineralizing ingredients onto tooth surfaces to effectextended remineralization of said tooth surfaces, with a minimum ofsaliva “wash-out” of said remineralizing ingredients.
 56. Improvedmethods for remineralizing, comprising treating tooth surfaces withcompositions that are substantive to tooth surfaces and that extend theduration of said improved, remineralizing methods, comprising: anaqueous-free emulsion containing dispensed therein variousremineralizing ingredients wherein: said aqueous-free emulsion in thepresence of saliva, forms a mucoadhesive gel substantive to said toothsurfaces, said substantive, mucoadhesive gel gradually dissolves in thepresence of saliva, releasing onto said tooth surfaces, saidremineralizing ingredients, and said slowly released remineralizingingredients continue to remineralize said tooth surfaces until saidsubstantive mucoadhesive gel is solubilized by said saliva flow, therebyextending the duration of said improved, remineralizing methods andeffecting improved remineralization of said tooth surfaces.
 57. Animproved method for remineralizing, comprising treating tooth surfaceswith compositions according to claim 56, wherein said remineralizingingredients are selected from the group consisting of: variousfluorides, various amorphous calcium phosphate fluoride combinations,bioglass, tricalcium phosphate fluoride mixtures and combinationsthereof.
 58. An improved method for remineralizing, comprising treatingtooth surfaces with compositions according to claim 56, wherein saidaqueous-free emulsion contains polydimethylsiloxane as the discontinuousphase and nonionic poloxamer surfactants as the continuous phase.
 59. Animproved method for remineralizing, comprising treating tooth surfaceswith compositions according to claim 58, wherein saidpolydimethylsiloxane discontinuous phase has a viscosity between about1500 cs and about 2.5 million cs.
 60. An improved method forremineralizing, comprising treating tooth surfaces with compositionsaccording to claim 58, wherein said nonionic surfactant continuous phasecomprises nonionic poloxamer surfactants that form mucoadhesive gels inthe presence of saliva, wherein said gels are substantive to toothsurfaces.
 61. An improved method for remineralizing, comprising treatingtooth surfaces with compositions according to claim 60, wherein saidnonionic surfactant is selected from the group consisting of:poloxamers, polysorbates, poloxyethylene alcohols and combinationsthereof.
 62. An improved method for remineralizing, comprising treatingtooth surfaces with compositions according to claim 57, wherein saidamorphous calcium phosphate fluoride combinations comprise mixturesselected from the group consisting of: calcium gluconate, calciumlactate gluconate, calcium nitrate, calcium sulfate and combinationsthereof.
 63. An improved method for remineralizing, comprising treatingtooth surfaces with compositions according to claim 55, whereindispensing means for said improved remineralizing compositions areselected from the group consisting of: interproximal devices coated withsaid compositions, prophy paste, varnish, gel, toothpaste, chewing gum,sealant, rinse, and combinations thereof.
 64. An improved method forremineralizing, comprising treating tooth surfaces with compositions ofthe invention according to claim 56, wherein the substantivity of saidmucoadhesive gel is improved by the addition of compositions selectedfrom the group consisting of: poloxamers, carboxymethyl cellulose,carbopol, gantrez, carrageenan gum, tragacanth gum, xanthan gum, guargum and combinations thereof.
 65. An improved method for remineralizing,comprising treating tooth surfaces with compositions according to claim62 wherein the pH of said amorphous calcium phosphate fluoridecombinations released onto tooth surfaces is adjusted by the addition ofpH control compositions selected from the group consisting of: citricacid, ascorbic acid, phosphoric acid, malic acid and combinationsthereof.
 66. An improved method for remineralizing, comprising treatingtooth surfaces with compositions according to claim 56 wherein saidsaliva flow is enhanced by the addition of saliva enhancing compositionsselected from the group consisting of: Jambu resin, spilanthes extract,spilanthol and combinations thereof.
 67. An improved method forremineralizing, comprising treating tooth surfaces with compositionsaccording to claim 55, wherein said mucoadhesive gels are as shown inFIG. 1 through 8 of the Drawings.
 68. An improved method forremineralizing, comprising treating tooth surfaces with compositionsaccording to claim 55, wherein said remineralizing ingredients includecommercial versions from the group consisting of: various fluorides,various ACPF mixtures, various bioglass fluoride mixtures, varioustricalcium phosphate fluoride mixtures and combinations thereof.